Table 4. Schedule of events during hospitalisation.
| Study item | Screening | Enrolment
Day 1 |
Day 2 | Day 3 | Day 7 | Day 14 * | Weekly till
hospital discharge |
Hospital
discharge |
Further
Hospitalisation |
|---|---|---|---|---|---|---|---|---|---|
| Visit window (days) | +3 | +3 | +3 | ||||||
| Screening Consent
(Uganda only) |
X | ||||||||
| Assess eligibility criteria | X | ||||||||
| Patient information and
enrolment consent |
X | ||||||||
| Clinical history and examination | |||||||||
| Past medical history | X | X | |||||||
| Medication review | X | X | X | X | X | X | X | X | X |
| Document HIV status | X | ||||||||
| Current symptoms | X | X | X | X | X | X | X | X | X |
| Physical examination | X | X | X | X | X | X | X | X | |
| GCS score a | X | X | X | X | X | X | X | X | X |
| BMRC disease grade | X | ||||||||
| Adverse event assessment | X | X | X | X | X | X | X | X | |
| Investigations | |||||||||
| HIV-test (if not known positive) | X | ||||||||
| Cryptococcal antigen if HIV+
(blood) |
X | ||||||||
| Sodium | X c | X g | X | X | |||||
| Potassium | X | ||||||||
| Glucose (bedside) | X c | ||||||||
| Creatinine d | X c | X g | X | X | |||||
| Hepatic panel e | X c | X g | X | X | X | ||||
| Blood Count (including
differential) |
X c | X g | X | X | |||||
| CD4 if HIV-positive | X c | X g | |||||||
| Pregnancy test | Women c | ||||||||
| Chest radiograph | +/- c | ||||||||
| Urine sample +/- storage f | X c | ||||||||
| Lumbar puncture for Xpert,
culture and storage after enrolment and if not contra- indicated (SA) h |
X | ||||||||
| PK/PD sub-study in
participating sites: sparse PK sampling g (plasma x3 and CSF x1 sample) |
X | ||||||||
| Blood / DNA / RNA storage | X | X (if RIF
PK) |
X (if ART
PK, or at hos d/c) |
Optional (with
consent) |
|||||
Footnotes:
*week 2 visit may be performed as an inpatient or outpatient depending on the time of hospital discharge
a GCS will be captured daily during hospitalisation on a log by study team or routine care providers
b Adverse events will be recorded according to DAIDS toxicity scale
c Provided as standard of care in some of the trial sites. Where not performed as part of SOC the test will be study sponsored.
d Additional renal monitoring will be undertaken in those with abnormal baseline creatinine
e Hepatic panel = alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin. Hepatitis BsAg, Hepatitis C Ab will be added if baseline ALT is elevated. In the event of DILI hepatic panel will be performed as per DILI SOP.
f Urine sample may be collected from HIV-positive patients during screening for testing with TB-LAM (lipoarobinmannan) as part of TB work-up
g Baseline bloods must occur at either during screening or at enrolment visit. It is possible these visits will be on the same day. If baseline bloods were done at screening and enrolment occurs >72 hours later baseline blood tests will be repeated.
h LP may be performed to do initial Xpert/TB culture tests (if not done through routine care) or to repeat these tests to improve diagnostic yield of TBM. Investigations requested by the treating physician as part of routine care (e.g. exclusion of additional causes of meningitis as appropriate) may also be performed on CSF obtained at this timepoint
GCS = Glasgow come scale, BMRC = British Medical Research Council, PK = pharmacokinetic, PD = pharmacodynamic.